Peng Anghui, Peng Wang, Wang Ruiqi, Zhao Hao, Yu Xinyang, Sun Yihao
Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China.
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China.
Front Cell Dev Biol. 2022 Jun 8;10:879465. doi: 10.3389/fcell.2022.879465. eCollection 2022.
Three-dimensional (3D) genomics is the frontier field in the post-genomics era, its foremost content is the relationship between chromatin spatial conformation and regulation of gene transcription. Cancer biology is a complex system resulting from genetic alterations in key tumor oncogenes and suppressor genes for cell proliferation, DNA replication, cell differentiation, and homeostatic functions. Although scientific research in recent decades has revealed how the genome sequence is mutated in many cancers, high-order chromosomal structures involved in the development and fate of cancer cells represent a crucial but rarely explored aspect of cancer genomics. Hence, dissection of the 3D genome conformation of cancer helps understand the unique epigenetic patterns and gene regulation processes that distinguish cancer biology from normal physiological states. In recent years, research in tumor 3D genomics has grown quickly. With the rapid progress of 3D genomics technology, we can now better determine the relationship between cancer pathogenesis and the chromatin structure of cancer cells. It is becoming increasingly explicit that changes in 3D chromatin structure play a vital role in controlling oncogene transcription. This review focuses on the relationships between tumor gene expression regulation, tumor 3D chromatin structure, and cancer phenotypic plasticity. Furthermore, based on the functional consequences of spatial disorganization in the cancer genome, we look forward to the clinical application prospects of 3D genomic biomarkers.
三维(3D)基因组学是后基因组时代的前沿领域,其首要内容是染色质空间构象与基因转录调控之间的关系。癌症生物学是一个复杂的系统,由关键肿瘤癌基因和抑癌基因在细胞增殖、DNA复制、细胞分化及稳态功能方面的基因改变所导致。尽管近几十年来的科学研究揭示了许多癌症中基因组序列是如何发生突变的,但参与癌细胞发生发展和命运的高阶染色体结构却是癌症基因组学中一个关键但很少被探索的方面。因此,剖析癌症的三维基因组构象有助于理解将癌症生物学与正常生理状态区分开来的独特表观遗传模式和基因调控过程。近年来,肿瘤三维基因组学的研究迅速发展。随着三维基因组学技术的快速进步,我们现在能够更好地确定癌症发病机制与癌细胞染色质结构之间的关系。越来越明确的是,三维染色质结构的变化在控制癌基因转录中起着至关重要的作用。本综述重点关注肿瘤基因表达调控、肿瘤三维染色质结构与癌症表型可塑性之间的关系。此外,基于癌症基因组空间紊乱的功能后果,我们展望了三维基因组生物标志物的临床应用前景。